One of the challenges that regenerative therapy faces is regeneration and restoration of nerve function damaged by various nervous system diseases, trauma and the like.
For example, a method is sought in which neuronal cells generated by in vitro culture systems are injected into affected sites to complement lost neuronal cells. However, even when neuronal cells which have already extended neuroaxes are injected to affected sites (such as the central nerve system tissue including brain), it is difficult to reconstruct the neural network as prior to being damaged. In addition, the central nerve system tissue particularly exhibits and maintains nerve functions by constituting the physiological environment in which neuronal cells and various other cells (such as astrocytes) interact, and thus it is difficult to restore the nerve function only by compensation of the neuronal cells.
Consequently, it is expected to establish the regeneration and restoration techniques of nerve function by utilizing neural stem cells. For example, it is expected to restore the nerve function by a therapeutic method in which neural stem cells are injected to affected sites (such as the central nerve system tissue including brain) or regeneration ability of the endogenous neural stem cells is utilized to allow differentiation in vivo (typically at the affected sites) of the stem cells to required cells (such as neuronal cells and astrocytes), thereby compensating lost cells and reconstructing the neural network and physiological environment.
It has been recently demonstrated that neural stem cells exist in the adult brain and when the brain is damaged, neuronal cells differentiated from the neural stem cells migrate towards the affected site (damaged site) and the neuronal cells grow at the affected site to mature neuronal cells to contribute to compensation of neuronal cells and reconstruction of the neural network (Non Patent Literature 1). However, differentiation of neural stem cells to neuronal cells in the adult brain has only been demonstrated in limited regions such as the subventricular zone (SVZ) region of the lateral ventricle or the subgranular zone (SGZ) region of the hippocampal dentate gyrus. It is also pointed out that the number of neural stem cells in the adult brain is low and the number of surviving neuronal cells differentiated from neural stem cells and migrated to the affected site is extremely low. From this reason, it is insufficient to regenerate and restore the nerve function only by spontaneous supply of neuronal cells by neural stem cells in the adult brain as described above. At present, no efficient means has been established that promotes in vivo differentiation of neural stem cells existing in the adult brain to required cells, migration of the cells to the affected site and further engraftment thereof at the affected site.
Meanwhile, neural stem cells injectable to affected sites may be obtained by methods such as the one in which neural stem cells in the foetal brain or in the early postnatal brain or neural stem cells in the adult brain are utilized or the one in which embryonic stem cells (ES cells) or induced pluripotent stem cells (iPS cells) are differentiated. However, the method utilizing neural stem cells in the brain or the method for differentiating ES cells have difficulties in terms of ethical problems and rejections. The method for differentiating induced pluripotent stem cells also has many challenges in terms of safety, efficiency and costs for practical application.